动物TRPM8受体低温敏感功能的获得机制研究

探究动物温度感知受体的功能演化是揭示动物环境温度适应机制的关键切入点。TRPM8是唯一被广泛证实的冷敏感受体，但是关于TRPM8的功能演化尚不完全清楚，阻碍了人类对动物低温感受调控多样性及其意义的认识。TRPM8的冷激活功能主要受两个关键结构域调控：其中，温度响应元件使TRPM8获得低温敏感的功能，而耦联结构域决定TRPM8的冷激活效率。在我们前期的工作中揭示了不同物种TRPM8耦联结构域的功能多样性及其生物学意义（PNAS, 2020），但尚未回答TRPM8低温敏感功能的获得机制（温度响应元件）。在本项目中，我们将识别TRPM8的温度响应元件，揭示其功能演化过程，探讨其功能多样性的生物学意义。目前，我们初步识别了TRPM8的温度响应元件并开展了部分功能多样性检测。因此，本项目有望通过对TRPM8温度响应元件功能演化的研究，揭示动物TRPM8低温敏感功能的获得机制及其生物学意义。

Exploring the functional evolution of animal temperature sensing receptor is the key point to reveal the mechanism of animal adaptation to environmental temperature. TRPM8 is the only widely recognized cold sensitive receptor. However, the functional evolution of TRPM8 is still unclear, which hinders the understanding of the regulatory diversity of animal cold sensing and its biological significance. The cold activation of TRPM8 is mainly regulated by two key domains: the temperature sensitive elements make TRPM8 obtain cold activation function, and the coupling domain determines the cold activation efficiency of TRPM8. In our previous work, we revealed the functional diversity of TRPM8 coupled domains in different species and its biological significance (PNAS, 2020). However, the evolution of TRPM8 cold activation has not been answered (temperature sensitive elements). In this project, we will focus on the functional evolution of the TRPM8 temperature sensitive elements and the biological significance of its functional diversity. Until now, we have preliminarily identified the TRPM8 temperature sensitive elements, and detected some functional diversity of this elements. Therefore, this project is expected to reveal the acquisition mechanism and biological significance of TRPM8 cold sensitive function by studying the functional evolution of the TRPM8 cold sensitive elements.